Nikhil Sharma - Academia.edu (original) (raw)

Papers by Nikhil Sharma

Ancient fluvial deposits typically display repetitive changes in their depositional architecture ... more Ancient fluvial deposits typically display repetitive changes in their depositional architecture such as alternating intervals of coarse-grained highly amalgamated (HA), laterally-stacked, channel bodies, and finer-grained less amalgamated (LA), vertically-stacked, channels encased in floodplain deposits. Such patterns are usually ascribed to slower, respectively higher, rates of base level rise (accommodation). However, “upstream” factors such as water discharge and sediment flux also play a potential role in determining stratigraphic architecture, yet this possibility has never been tested despite the recent advances in the field of palaeohydraulic reconstructions from fluvial accumulations. Here, we chronicle riverbed gradient evolution within three Middle Eocene (~ 40 Ma) fluvial HA-LA sequences in the Escanilla Formation in the south-Pyrenean foreland basin. This work documents, for the first time in a fossil fluvial system, how the ancient riverbed systematically evolved from ...

Cureus, Jan 27, 2018

Intracranial dural arteriovenous fistulae (DAVF) are rare vascular malformations. They are genera... more Intracranial dural arteriovenous fistulae (DAVF) are rare vascular malformations. They are generally considered to be acquired lesions, often attributed to dural sinus thrombosis and intracranial venous hypertension. The authors encountered a case of DAVF associated with an octreotide-positive vestibular schwannoma. A 46-year-old female had symptoms of right ear congestion accompanied by pulsatile tinnitus and mild hearing loss. Magnetic resonance imaging (MRI) identified a lobulated mass centered at the cerebellopontine angle. Preoperatively, on cerebral angiography, there was an incidental discovery of a DAVF in the right posterior fossa. The decision was made to proceed with resection of the tumor in a staged fashion. Her latest follow-up MRI showed no evidence of recurrent tumor. This is the second reported case of DAVF associated with an intracranial schwannoma. Findings are discussed along with a thorough review of the literature. This case, combined with the data from the lit...

Journal of orthopaedics, 2018

We report outcomes of using GraftJacket to repair massive rotator-cuff-tears. Twenty patients wit... more We report outcomes of using GraftJacket to repair massive rotator-cuff-tears. Twenty patients with a mean age of 64.6y over 12-month duration were reviewed. Two patients had a single GraftJacket repair (group1), whilst 18 had the GraftJacket sheet doubled (group2). Pre and post oxford shoulder scores (OSS) and patient related outcome measures were evaluated. A statistically significant improvement of OSS was demonstrated in-group 2 from a mean of 22 to 45.5 (p < 0.00148) over a follow up of 18 months. GraftJacket is a safe and effective procedure to use as an interpositional graft and doubling the graft may improve outcomes.

Proceedings of the National Academy of Sciences of the United States of America, Jan 29, 2008

Renal tubule epithelial cells express the insulin receptor (IR); however, their value has not bee... more Renal tubule epithelial cells express the insulin receptor (IR); however, their value has not been firmly established. We generated mice with renal epithelial cell-specific knockout of the IR by Cre-recombinase-loxP recombination using a kidney-specific (Ksp) cadherin promoter. KO mice expressed significantly lower levels of IR mRNA and protein in kidney cortex (49-56% of the WT) and medulla (32-47%) homogenates. Immunofluorescence showed the greatest relative reduction in the thick ascending limb and collecting duct cell types. Body weight, kidney weight, and food and water intakes were not different from WT littermates. However, KO mice had significantly increased basal systolic blood pressure (BP, 15 mm Hg higher) as measured by radiotelemetry. In response to a volume load by gavage (20 ml/kg of body weight, 0.9% NaCl, 15% dextrose), KO mice had impaired natriuresis (37 +/- 10 versus 99 +/- 9 mmol of Na(+) per 2 h in WT). Furthermore, volume load led to a sustained increase in BP...

Virology, 2006

The gammaherpesviruses Rhesus lymphocryptovirus (LCV) and Epstein-Barr virus (EBV) are closely re... more The gammaherpesviruses Rhesus lymphocryptovirus (LCV) and Epstein-Barr virus (EBV) are closely related phylogenetically. Rhesus LCV efficiently immortalizes Rhesus B cells in vitro. However, despite a high degree of conservation between the Rhesus LCV and EBV genomes, Rhesus LCV fails to immortalize human B cells in vitro. This species restriction may, at least in part, be linked to the EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), known to be essential for B cell transformation. We compared specific properties of EBNA3C, a well-characterized and essential EBV protein, with its Rhesus counterpart to determine whether EBNA3C phenotypes which contribute to cell cycle regulation are conserved in the Rhesus LCV. We show that both EBNA3C and Rhesus EBNA3C bind to a conserved region of mammalian cyclins, regulate pRb stability, and modulate SCF Skp2-dependent ubiquitination. These results suggest that Rhesus LCV restriction from human B cell immortalization is independent of the conserved cell cycle regulatory functions of the EBNA3C protein.

Neuron, 2010

We report a role for long-distance retrograde neurotrophin signaling in the establishment of syna... more We report a role for long-distance retrograde neurotrophin signaling in the establishment of synapses in the sympathetic nervous system. Target-derived NGF is both necessary and sufficient for formation of postsynaptic specializations on dendrites of sympathetic neurons. This, in turn, is a prerequisite for formation of presynaptic specializations, but not preganglionic axonal ingrowth from the spinal cord into sympathetic ganglia. We also find that NGF-TrkA signaling endosomes travel from distal axons to cell bodies and dendrites where they promote PSD clustering. Furthermore, the p75 neurotrophin receptor restricts PSD formation, suggesting an important role for antagonistic NGF-TrkA and p75 signaling pathways during retrograde control of synapse establishment. Thus, in addition to defining the appropriate number of sympathetic neurons that survive the period of developmental cell death, target-derived NGF also exerts control over the degree of connectivity between the spinal cord and sympathetic ganglia through retrograde control of synapse assembly.

Journal of Virology, 2004

The Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is a virus-encoded latent antigen essent... more The Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is a virus-encoded latent antigen essential for primary B-cell transformation. In this report we demonstrate that although the carboxy terminus of EBNA3C predominantly regulates cyclin A-dependent kinase activity, the region of greatest affinity for cyclin A lies within the EBNA3 amino-terminal homology domain of EBNA3C. Detailed mapping studies employing both in vitro binding assays and coimmunoprecipitation experiments implicated a small region of EBNA3C, amino acids 130 to 159 within the EBNA3 homology domain, as having the greatest affinity for cyclin A. The EBNA3 homology domain has the highest degree of amino acid similarity (approximately 30%) between the EBNA3 proteins, and, indeed, EBNA3B, but not EBNA3A, showed binding activity with cyclin A. We also show that EBNA3C binds to the α1 helix of the highly conserved mammalian cyclin box, with cyclin A amino acids 206 to 226 required for strong binding to EBNA3C amino aci...

Journal of Stroke and Cerebrovascular Diseases, 2014

Background: Patients and carers increasingly access the Internet as a source of health informatio... more Background: Patients and carers increasingly access the Internet as a source of health information. Poor health literacy is extremely common and frequently limits patient's comprehension of health care information literature. We aimed to assess the readability of online consumer-orientated stroke information using 2 validated readability measures. Methods: The 100 highest Google ranked consumer-oriented stroke Web pages were assessed for reading difficulty using the Flesch-Kincaid and Simple Measure of Gobbledygook (SMOG) formulae. Results: None of the included Web pages complied with the current readability guidelines when readability was measured using the gold standard SMOG formula. Mean Flesch-Kincaid grade level was 10.4 (95% confidence interval [CI] 9.97-10.9) and mean SMOG grade 12.1 (95% CI 11.7-12.4). Over half of the Web pages were produced at graduate reading levels or above. Not-for-profit Web pages were significantly easier to read (P 5 .0006). The Flesch-Kincaid formula significantly underestimated reading difficulty, with a mean underestimation of 1.65 grades (95% CI 1.49-1.81), P , .0001. Conclusions: Most consumer-orientated stroke information Web sites require major text revision to comply with readability guidelines and to be comprehensible to the average patient. The Flesch-Kincaid formula significantly underestimates reading difficulty, and SMOG should be used as the measure of choice.

Journal of Neurology, Neurosurgery & Psychiatry, 2010

International Journal of Surgery, 2013

8.3%(1/12) with the same patient suffering SCI. The stroke rate was 0%(0/12). In 75%(9/12) of cas... more 8.3%(1/12) with the same patient suffering SCI. The stroke rate was 0%(0/12). In 75%(9/12) of cases, traditional access was contraindicated by iliac disease and the remainder because of an existing ligated aortic stump(8.3%) or the need to access the ascending aorta(16.7%). 83%(10/12) of patients were unfit for open procedure. 50%(6/12) of patients were considered for subclavian/axillary access with data unavailable for the remainder. Of those considered, 50%(3/12) had vessels too small and the remainder conduits for pre-existing grafts or occluded. Conclusion: Although there is a relative paucity of literature, this study demonstrates when traditional endovascular access is impossible and an open procedure contraindicated, carotid artery access is a viable alternative with excellent 30-day survival and low rates of neurological sequelae.

Stroke, 2014

Background: Clopidogrel is a thienopyridine with ADP antagonising effects that is widely used in ... more Background: Clopidogrel is a thienopyridine with ADP antagonising effects that is widely used in the secondary prevention of ischemic strokes and transient ischemic attacks (TIAs). Despite this some patients will go on to have recurrent strokes or TIAs. Cardiology trials have identified patients with clopidogrel resistance, defined as a vasodilator-stimulated phosphoprotein (VASP) index of >50% after at least 7 days of clopidogrel treatment. This was associated with recurrent cardiac events. The VASP-index measures phosphorylation of VASP in the resting state and activated states using flow cytometry techniques. As phosphorylation of VASP is dependent upon activation of the platelet P2Y12 receptor that is targeted by clopidogrel the difference in phosphorylation between the two states provides an indirect measure of platelet inhibition. Previous trials have shown a prevalence of clopidogrel resistance in stroke patients of between 8 and 18%, but no study to date has shown whether...

Stroke, 2009

Background and Purpose— In recovered subcortical stroke, the pattern of motor network activation ... more Background and Purpose— In recovered subcortical stroke, the pattern of motor network activation during motor execution can appear normal or not, depending on the task. Whether this applies to other aspects of motor function is unknown. We used functional MRI to assess motor imagery (MI), a promising new approach to improve motor function after stroke, and contrasted it to motor execution. Methods— Twenty well-recovered patients with hemiparetic subcortical stroke (14 males; mean age, 66.5 years) and 17 aged-matched control subjects were studied. Extensive behavioral screening excluded 8 patients and 4 control subjects due to impaired MI abilities. Subjects performed MI and motor execution of a paced finger–thumb opposition sequence using a functional MRI paradigm that monitored compliance. Activation within the primary motor cortex (BA4a and 4p), dorsal premotor, and supplementary motor areas was examined. Results— The pattern of activation during affected-hand motor execution was ...

It is a review article on the topic of energy harvesting.

Cureus, 2021

Introduction Vancomycin may be used as an alternative perioperative antibiotic for penicillin-all... more Introduction Vancomycin may be used as an alternative perioperative antibiotic for penicillin-allergic patients but follows a different infusion timing. At the institution presented herein, noncompliance with recommended vancomycin infusion timing has been hypothesized to contribute toward increased risk of surgical site infections and avoidable expenditures. The objective of this project was to utilize the Performance Improvement In Action methodology to identify, address, and solve the problem of vancomycin administration timing. Methodology This study took place at a multi-hospital, urban academic medical center. The protocol was developed by neurosurgery and anesthesia faculty, advanced practice providers, nursing, and pharmacy. Timing of the following points was recorded: initial order, order release, pharmacy verification, vancomycin infusion, and surgical incision. Fifty consecutive penicillin-allergic patients undergoing neurosurgical intervention were prospectively enrolled. Data comparison was made between the pilot and retrospective review cohorts. Results The pilot cohort achieved correct administration of vancomycin in 100% of cases. Average infusion start time prior to incision increased by 257% (p<0.0001). Conclusions This study demonstrates a departmental capacity for optimized timing of vancomycin infusions, in a budget-and workflow-neutral process, while reducing inappropriate administration. In the future, this protocol may be scaled to additional departments and institutions to appropriately and efficiently administer perioperative vancomycin and mitigate the risk for surgical site infections.

Journal of affective disorders, Dec 30, 2018

Affective problems increase the risk of dementia and cognitive impairment, yet the life course di... more Affective problems increase the risk of dementia and cognitive impairment, yet the life course dimension of this association is not clearly understood. We aimed to investigate how affective problems across the life course relate to later-life cognitive state. Data from 1269 participants from the Medical Research Council National Survey of Health and Development (NSHD, the British 1946 birth cohort) were used. Prospectively-assessed measures of affective symptoms spanning ages 13-69 and categorised into case-level thresholds. Outcomes consisted of a comprehensive measure of cognitive state (Addenbrooke's Cognitive Examination (ACE-III)), verbal memory, and letter search speed and accuracy at age 69. Complementary life course models demonstrated that having 2 or more case-level problems across the life course was most strongly associated with poorer cognitive outcomes, before and after adjusting for sex, childhood cognition, childhood and midlife occupational position and educatio...

BMC neurology, Jan 18, 2017

Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the c... more Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment - including β-amyloid depostion, vascular disease, network breakdown and atrophy - to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms. This paper outlines the clinical, cognitive and imaging protocol of…

BioMed Research International, 2017

Next-generation DNA sequencing (NGS) has made it feasible to sequence large number of microbial g... more Next-generation DNA sequencing (NGS) has made it feasible to sequence large number of microbial genomes and advancements in computational biology have opened enormous opportunities to mine genome sequence data for novel genes and enzymes or their sources. In the present communication in silico mining of microbial genomes has been carried out to find novel sources of nitrilases. The sequences selected were analyzed for homology and considered for designing motifs. The manually designed motifs based on amino acid sequences of nitrilases were used to screen 2000 microbial genomes (translated to proteomes). This resulted in identification of one hundred thirty-eight putative/hypothetical sequences which could potentially code for nitrilase activity. In vitro validation of nine predicted sources of nitrilases was done for nitrile/cyanide hydrolyzing activity. Out of nine predicted nitrilases, Gluconacetobacter diazotrophicus, Sphingopyxis alaskensis, Saccharomonospora viridis, and Shimwe...

European journal of epidemiology, Nov 1, 2016

A life course approach to ageing relies on maintaining participation rates in national birth coho... more A life course approach to ageing relies on maintaining participation rates in national birth cohorts and other long-term longitudinal studies. This reduces the risk of selective attrition biasing associations between lifetime risk factors and health outcomes in later life and ensures the studies remain as representative as possible of the original population. We report the participation patterns for a postal questionnaire and home visit at 68-69 years of study members in the MRC National Survey of Health and Development, the oldest and longest-running British birth cohort study. We investigated how participation varied by lifetime and recent contact, health status, previous clinical feedback and study engagement, taking account of prior socioeconomic and cognitive characteristics. Overall participation and home visit participation remained high (94 and 80%, respectively) and there were no gender differences. Participation was higher in those with higher levels of prior contact and l...